Study in Non-Clear Cell Renal Carcinoma (Ncc-RCC) Temsirolimus Versus Sunitinib

Prospective Randomized Phase-II Trial With Temsirolimus Versus Sunitinib in Previously Untreated Patients With Advanced or Metastatic Non-Clear Cell Renal Carcinoma

This will be a prospective, open-label, randomized multicenter phase-II study to evaluate progression free survival (PFS) in patients with locally advanced or metastatic non-clear cell renal cell cancer (ncc-RCC) receiving Temsirolimus in comparison to Sunitinib.

In most clinical trials in renal cell carcinoma (RCC), clear cell RCC have been included exclusively. There are only some limited data on the efficacy of Temsirolimus or Sunitinib in ncc-RCC showing interesting response rates for both agents. However, randomized clinical trials in this specific patient population have not yet been performed.

In the proposed study a comparison Temsirolimus and Sunitinib is scheduled in first line therapy of ncc-RCC.

Study Overview

• Status: Completed
• Conditions: Non-clear Cell Renal Cell Cancer
• Intervention / Treatment: Drug: Temsirolimus; Drug: Sunitinib

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany
    • Vivantes Klinikum Am Urban
  • Berlin, Germany
    • Charité - Campus Virchow Klinikum
  • Berlin, Germany
    • Charité - Mitte
  • Bonn, Germany
    • Evangelische Kliniken Bonn gGmbH - Johanniter-Krankenhaus
  • Düsseldorf, Germany
    • Universitatsklinikum Dusseldorf
  • Essen, Germany
    • Universitätsklinikum Essen
  • Frankfurt, Germany
    • Klinikum der J.W. Goethe Universität
  • Halle, Germany
    • Martin-Luther-Universität Halle-Wittenberg
  • Jena, Germany
    • Universitätskrankenhaus Jena
  • Lübeck, Germany
    • UK-SH Campus Lübeck
  • Oldenburg, Germany
    • Klinikum Oldenburg gGmbH
  • Stuttgart, Germany
    • Klinikum Stuttgart, Katharinenhospital
  • Viersen, Germany
    • Facharzt für Innere Medizin,
  • Weiden, Germany
    • Kliniken Nordoberpfalz AG - Klinikum Weiden

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult males and females: ≥18 years of age.
2. Locally advanced or metastatic, histological confirmed, non-clear cell RCC of all subtypes. Patients must have advanced non-clear cell of one of the following subtypes: papillary, chromophobe, collecting duct carcinoma (CDC), renal medullary carcinoma (RMC), or unclassified.
3. Patients with measurable disease (at least one uni-dimensionally measurable target lesion by CT-scan or MRI) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) If prior palliative radiotherapy to metastatic lesions: ≥ 1 measurable lesion that has not been irradiated.
4. PS 0-2 ECOG
5. Signed written informed consent.
6. White blood cell count (WBC) ≥4x10*9/L with neutrophils ≥1.5 x 10*9/L, platelet count ≥100x10*9/L, hemoglobin ≥9 g/dL.]
7. Total bilirubin <2 x upper limit of normal.
8. AST and ALT <2.5 x upper limit of normal, or <5 x upper limit of normal in case of liver metastases.
9. Serum creatinine <2.0 x upper limit of normal.
10. Normal ECG without QT prolongation (QTc < 450msec).
11. Adequate cardiac function (left ventricular ejection fraction > 40% as assessed by ECHO.

Exclusion Criteria:

1. Predominant clear-cell RCC
2. Resectability or other curative options
3. Any investigational drug within the 30 days before inclusion.
4. Prior systemic treatment for their RCC.
5. Known or suspected allergy or hypersensitivity reaction to any of the components of study treatments.
6. Radiotherapy within the last 4 weeks.
7. Pregnancy (absence to be confirmed by beta-hCG test) or lactation period.
8. Men or women of child-bearing potential who are sexually active and unwilling to use a medically acceptable method of contraception during the trial.
9. Clinically symptomatic brain or meningeal metastasis. (known or suspected)
10. Cardiac arrhythmias requiring anti-arrhythmics (excluding beta blockers or digoxin).

11. History of any of the following cardiac events within the past 6 months:

    • myocardial infarction (including severe/unstable angina),
    • coronary/peripheral artery bypass graft,
    • congestive heart failure (CHF),
    • cerebrovascular accident,
    • transient ischemic attack,
    • pulmonary embolism.
12. No hemorrhage ≥ grade 3 within the past 4 weeks
13. Uncontrolled severe hypertension (failure of diastolic blood pressure to fall below 90 mm Hg despite the use of ≥3 anti-hypertensive drugs
14. History of relevant pulmonary hypertension or interstitial lung disease.
15. Acute or sub-acute intestinal occlusion or history of inflammatory bowel disease or chronic diarrhea
16. Previous malignancy (other than renal cancer cancer) in the last 5 years except basal cell cancer of the skin, pre-invasive cancer of the cervix or superficial bladder tumor [Ta, Tis and T1].
17. History of organ allograft
18. Significant disease which, in the investigator's opinion would exclude the patient from the study
19. Patients with seizure and epileptic disorder or other conditions requiring medication (such as phenytoin, carbamazepin, phenobarbital)
20. Patients under strong inducers or inhibitors to CYP Isoenzymes
21. Patients with hypersensitivity to the antihistamine or patients who cannot receive the antihistamine for other medical reasons
22. Patients requiring long-term cortisone therapy
23. Patients requiring oral anticoagulation treatment, such as marcoumar. (Anticoagulation treatment with heparin or low molecular weight heparin [LMWH] is allowed provided that close monitoring is performed).
24. Surgery within at least 2 weeks prior to randomization
25. HIV seropositivity.
26. Abnormal pulmonary function (DLCO < 50%). [Pulmonary function tests need only to be performed if abnormal pulmonary function present in medical history].
27. Poorly controlled diabetes mellitus.
28. Liver cirrhosis, chronic hepatitis
29. Legal incapacity or limited legal capacity
30. Known alcohol or drug abuse.
31. Medical or psychological conditions that would not permit the patient to complete the study or sign informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; Temsirolimus	Drug: Temsirolimus; 25 mg intravenously, once weekly infusion
Experimental: B; Sunitinib	Drug: Sunitinib; 50 mg oral once daily for 4 weeks, followed by 2 weeks rest.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to progression	7-11 months expected

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective response	7-11 months expected
safety assessed using CTCAE v3.0 and safety assessed according to reported SAEs	8-12 months (treatment duration + 1 months)
one year progression free survival rate (1YPFSR)	1 year
overall survival (OS)	will be evaluated in 2013

Collaborators and Investigators

• Sponsor: Central European Society for Anticancer Drug Research

Publications and helpful links

Helpful Links

• German description on the CESAR homepage

Study record dates

Study Major Dates

• Study Start: July 1, 2009
• Primary Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: September 9, 2009
• First Submitted That Met QC Criteria: September 17, 2009
• First Posted (Estimate): September 18, 2009

Study Record Updates

• Last Update Posted (Estimate): July 10, 2012
• Last Update Submitted That Met QC Criteria: July 6, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: Locally advanced or metastatic non-clear cell renal cell cancer (ncc-RCC)
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Protein Kinase Inhibitors; Antibiotics, Antineoplastic; Antifungal Agents; Sunitinib; Sirolimus
• Other Study ID Numbers: C-II-006 / 2009-010143-13